Resistance vs. Aerobic Training on Breast Cancer Patients Undergoing Neoadjuvant Treatment

NCT ID: NCT05297773

Last Updated: 2025-02-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

132 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-16

Study Completion Date

2025-12-30

Brief Summary

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A recent consensus study suggested that understanding the impact of exercise on the tumor microenvironment and therapy effectiveness is paramount and should be considered as a research priority. Therefore, the research team intends to address some of the scientific challenges proposed, which represent clear gaps in the current knowledge.

The investigators propose a randomized controlled trial conducted during all neoadjuvant treatment duration that aims to evaluate and compare the effects of two different exercise protocols (aerobic and resistance training) against a relaxation control group on Ki-67% changes as the main outcome in breast cancer patients. Secondary outcomes will be body composition; resting metabolic rate; physical fitness; quality of life, fatigue, depression/anxiety; accelerometry data (physical activity levels, sedentary time); sleep quality; tumor biology (size, hypoxia, and immune profile); glycemic, lipid, and inflammatory profile.

This project will help not only researchers with the design of future exercise intervention protocols but will also help exercise physiologists in the decision-making process when defining training programs. Moreover, the investigators expect that this research program will encourage more cancer patients to exercise. The team expects that patients with breast cancer engaging in structured exercise will show a more marked decrease in Ki-67, tumor size, and hypoxia and increase the tumor-infiltrating lymphocytes (TILs) compared to controls. The investigators anticipate a more noticeable decrease in the preoperative endocrine prognostic index (PEPI) score and in the Residual Breast Cancer (RCB) in both training groups (respectively with hormonal and chemotherapy). Also, frequent declines in physical fitness are expected to be mitigated in exercisers. It is hypothesize that aerobic training will ameliorate cardiorespiratory fitness and fat mass, while the effects of resistance training will be more relevant for muscle strength, muscle mass, and bone health. Both exercise groups will show greater improvements in quality of life, fatigue, depression, anxiety, and sleep quality. Regarding glycemic, lipid, and inflammatory profiles, the investigators expect to see more favorable changes in both training groups, with a more evident decrease in fasting glucose and insulin, HbA1c%, total and LDL-cholesterol, and triglycerides, and the increase in HDL-cholesterol. The increase in C-reactive protein (CRP), tumor necrosis factor -α (TNF-α), interleukin-6 (IL-6), IL-8, IL-1β, IL-1ra, and insulin-like growth factor-1 (IGF-1) and the decrease in brain-derived neutrotophic factor (BDNF), IL-12p70, IL-10, oncostatin M will be smaller in exercise groups.

Detailed Description

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Exercise plays a crucial role in breast cancer prevention and more recently it appears as a safe, non-pharmacological, and cost-effective adjuvant therapy for cancer. Indeed exercise improves the quality of life, fatigue, physical fitness, and also has a positive impact on tumor intrinsic characteristics.

Most of the studies regarding the effects of exercise in breast cancer patients were performed after surgery or in survivors. Despite being a window of opportunity to study the impact of exercise on biological properties of the tumor, namely on proliferation markers, the investigations conducted during the neoadjuvant period are still scarce and most of the literature derives from animal studies. Although originating from pilot investigations, the initial human-based evidence suggests that exercise interventions are feasible during neoadjuvant therapy and can potentially reduce some proliferation markers such as Ki-67 (i.e. a widely used prognostic marker), induce favorable changes in tumor-related genes, and increase survival.

Power and sample calculations (G-Power, Version 3.1.9.2) are based on an effect size of 0.25 for KI-67 while using ANOVA - repeated measures within-between interactions, a power of 0.80, a significance of 0.05, and an expected dropout of 40%. The calculation yielded a total sample size of 120 participants (60 undergoing chemotherapy and 60 undergoing hormone therapy: 20 participants per group per each treatment). The power and sample calculations were performed using a study that reported the effect of medication on KI-67 since no study has evaluated the effects of an exercise intervention on that variable and has obtained significant results.

Participants will be recruited to take part in an intervention study for breast cancer patients undergoing neoadjuvant treatment. The recruitment will take place at Champalimaud Clinical Center Breast Unit / Champalimaud Foundation.

To improve exercise adherence, the following strategies will be implemented:

* Thematic sessions about several topics such as physical activity (PA) guidelines, active lifestyle, nutrition, the benefits of exercise for breast cancer patients, etc. Each session will last 1-hour (30 minutes presentation + 30 minutes discussion/questions) and will occur once a month. These thematic sessions are mandatory.
* Group activities: once a month, a group activity will be promoted (exercise outdoor sessions, group walk, group dinner, etc.). In these group activities, participants may invite family members to participate.
* The NEO-program website presenting the mission/goals, team members, activities, news and events, contacts, etc.
* Facebook and Instagram account (share information and photos); before the intervention, written consent for image collection will be requested.

The investigator records clinical data, using a paper or electronic case report form (CRF), all data is collected in an online database that is available through the Champalimaud Clinical Center intranet. Participating physicians have a personal account to log in to the registration page and access the electronic CRF. They will have permanent access to their series of patients.

The participating physician ensures the confidentiality, accuracy, completeness, legibility, and timeliness of the data recorded. Data handling and statistical analysis will be done anonymously by the investigator, with the subject identification code list only available to the local investigator (and research nurse if applicable) working in the local center. The code will be based on the birth date and center abbreviation (and not patient initials). The Sponsor will be the owner of the data. Data will be kept for 20 years.

The Participating Investigator and the Participating Site shall treat all information and data relating to the Study disclosed to Participating Site and/or Investigator in this study as confidential and shall not disclose such information to any third parties or use such information for any purpose other than the performance of the Study.

The collection, processing, and disclosure of personal data, such as patient health and medical information are subject to compliance with applicable personal data protection and the processing of personal data legislation (including but not limited to the European Union Directive 95/46/EC).

Champalimaud Foundation takes out the appropriate insurance.

Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants will be followed in a randomized controlled trial conducted during the full duration of neoadjuvant treatment (i.e. 4- to 6-months, depending on patient treatment plan) and two cohorts will be defined: A - breast cancer patients undergoing chemotherapy; B - breast cancer patients undergoing endocrine therapy. Within each cohort, the participants will be divided into three groups: 1) aerobic training; 2): resistance training; 3): control group.

The intervention is designed to have equal energy expenditure throughout the exercise sessions in both exercise groups (10 kcal/kg/week). All training groups will complete 3 sessions/week. To ensure that both exercise groups are isoenergetic, a portable gas analyzer will be used and blood lactate will be collected.

Mandatory thematic sessions about several topics such as physical activity guidelines, active lifestyle will be implemented.
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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Aerobic Training

Three sessions per week during 4-6-months according to each individual treatment plan. Participants allocated in this group will perform moderate-to-vigorous intensity cycling exercise.

Group Type EXPERIMENTAL

Aerobic Training Group

Intervention Type BEHAVIORAL

The participants will perform continuous cycling at 30%-35% of their heart rate reserve for one month (phase 1: adaptive phase). Then, the intensity will increase every 4-5 weeks (± 5%) up to 80% of heart rate reserve (moderate intensity), depending on the participant's tolerance. An individualized equation establishing the relationship between heart rate, oxygen consumption, and power output will be determined during the cardiorespiratory fitness assessment and used to determine exercise intensity.

Resistance training

Three sessions per week during 4-6-months according to each individual treatment plan. Participants allocated in this group will perform weight-machine strength exercises of the upper and lower body.

Group Type EXPERIMENTAL

Resistance Training Group

Intervention Type BEHAVIORAL

Initially, and during the first two weeks of the adaptive phase (1-month), the resistance training group will perform one set of 8-12 repetitions (40%-repetition maximum) of 8 exercises for upper and lower body (squat, leg extension, leg curl, deadlift, plank, dead bug, seated row, shoulder press). Then, in the last two weeks, the participants will perform 2 sets of each exercise (45%-repetition maximum). After the adaptive phase, three sets of each exercise will be performed. The initial load will be 50% -repetition maximum increasing up to a maximum of 70%-repetition maximum at the end of the study. Every 4-5 weeks the load will be reviewed and adjusted according to individual.

Control Group

One session per week of relaxation/stretching.

Group Type ACTIVE_COMPARATOR

Control group

Intervention Type OTHER

The control group will perform a weekly stretching/relaxation session for 45 minutes.

Interventions

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Aerobic Training Group

The participants will perform continuous cycling at 30%-35% of their heart rate reserve for one month (phase 1: adaptive phase). Then, the intensity will increase every 4-5 weeks (± 5%) up to 80% of heart rate reserve (moderate intensity), depending on the participant's tolerance. An individualized equation establishing the relationship between heart rate, oxygen consumption, and power output will be determined during the cardiorespiratory fitness assessment and used to determine exercise intensity.

Intervention Type BEHAVIORAL

Resistance Training Group

Initially, and during the first two weeks of the adaptive phase (1-month), the resistance training group will perform one set of 8-12 repetitions (40%-repetition maximum) of 8 exercises for upper and lower body (squat, leg extension, leg curl, deadlift, plank, dead bug, seated row, shoulder press). Then, in the last two weeks, the participants will perform 2 sets of each exercise (45%-repetition maximum). After the adaptive phase, three sets of each exercise will be performed. The initial load will be 50% -repetition maximum increasing up to a maximum of 70%-repetition maximum at the end of the study. Every 4-5 weeks the load will be reviewed and adjusted according to individual.

Intervention Type BEHAVIORAL

Control group

The control group will perform a weekly stretching/relaxation session for 45 minutes.

Intervention Type OTHER

Other Intervention Names

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AT, moderate continuous cycling RT, machine-weight training Relaxation/stretching group

Eligibility Criteria

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Inclusion Criteria

* Histologically breast cancer (stage 0-III); scheduled for neoadjuvant treatment (cohort A - chemotherapy; cohort B - endocrine therapy)
* Women aged ≥ 18 years; nonpregnant
* Do not be involved in any structured exercise program in the past 6 months
* Medical approval to participate in the study
* Willingness to attend exercise sessions

Exclusion Criteria

* Treated for any cancer in the past 5 years (except basal cancer)
* Uncontrolled heart disease (heart failure, uncontrolled coronary heart disease, and uncontrolled hypertension, cardiac disease)
* Diabetes mellitus
* Lung condition (chronic obstructive or restrictive pulmonary disease)
* Psychological disorders (dementia, Alzheimer, and Parkinson Disease)
* Severe disability, or other medical condition that prevents from exercise training
* Alcohol or drugs abuse
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Faculdade de Motricidade Humana - Universidade de Lisboa

UNKNOWN

Sponsor Role collaborator

Fundacao Champalimaud

OTHER

Sponsor Role lead

Responsible Party

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Maria-Joao Cardoso

Head Breast Surgeon - Medical Doctor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Inês R. Correia, MSc

Role: STUDY_CHAIR

Faculdade de Motricidade Humana - Universidade de Lisboa

Locations

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Faculdade de Motricidade Humana - Universidade de Lisboa

Lisbon, Cruz-Quebrada, Portugal

Site Status ACTIVE_NOT_RECRUITING

Fundação Champalimaud

Lisbon, Lisbon District, Portugal

Site Status RECRUITING

Countries

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Portugal

Central Contacts

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Maria-João Cardoso, MD

Role: CONTACT

+351 210400200

Luís B Sardinha, Ph.D.

Role: CONTACT

+351 214149116 ext. 475291

Facility Contacts

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Maria João Cardoso, MD

Role: primary

+351 210480200

André Valente, Ph.D.

Role: backup

+351 210480200

References

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Ernst M, Wagner C, Oeser A, Messer S, Wender A, Cryns N, Brockelmann PJ, Holtkamp U, Baumann FT, Wiskemann J, Monsef I, Scherer RW, Mishra SI, Skoetz N. Resistance training for fatigue in people with cancer. Cochrane Database Syst Rev. 2024 Nov 28;11(11):CD015518. doi: 10.1002/14651858.CD015518.

Reference Type DERIVED
PMID: 39606939 (View on PubMed)

Other Identifiers

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NEO-Program

Identifier Type: OTHER

Identifier Source: secondary_id

Neo-program 2021.02.23

Identifier Type: -

Identifier Source: org_study_id

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